Journal of Clinical Immunology

, Volume 36, Issue 5, pp 423–428 | Cite as

A Difficult and Rare Diagnosis of Autoimmune Enteropathy in a Patient Affected by Down Syndrome

  • Anne Depince-Berger
  • Clara Cremilieux
  • Melanie Rinaudo-Gaujous
  • Christian Genin
  • Benedicte de Freminville
  • Claude Lambert
  • J. Bruneau
  • Stephane Paul
Letter to Editor


Patients with Down syndrome are more susceptible to autoimmune pathologies, in particular endocrine or digestive diseases such as celiac disease. Autoimmune enteropathy is another form of digestive autoimmune disease, non-gluten-dependant, more often diagnosed in male neonates with immunodysregulation and polyendocrinopathy such as the Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome. It also exists in the adult, but this pathology is less known and therefore frequently under-diagnosed. Clinical manifestations are similar to celiac disease, but not improved after a gluten-free diet. Autoimmune enteropathy is frequently associated with other autoimmune diseases, such as thyroiditis, myasthenia gravis, lupus or immune deficiencies, as Common Variable Immunodeficiency. Pathological analysis of intestinal biopsies can frequently distinguish autoimmune enteropathy and celiac disease. Autoimmune enteropathy usually has an important lymphoplasmacytic infiltration of the mucosa and a lack of intraepithelial lymphocytes in the gastrointestinal mucosal surface, while celiac disease usually has a polymorph infiltration of the mucosa and an important intraepithelial lymphocytes infiltration. Nevertheless, the two pathological patterns may overlap. Here we report the first case of a patient with Down syndrome associated to autoimmune enteropathy (initially diagnosed as celiac disease), chronic pancreatitis and cutaneous lupus erythematosus. Even if autoimmune pathologies are much more common in patients with Down syndrome, we would like to report on this rare and original association found in our patient.


Down syndrome immunity immunodeficiency autoimmune enteropathy celiac disease 


  1. 1.
    Sherman SL, Allen EG, Bean LH, Freeman SB. Epidemiology of down syndrome. Ment Retard Dev Disabil Res Rev. 2007;13(3):221–7.CrossRefPubMedGoogle Scholar
  2. 2.
    Carnicer J, Farré C, Varea V, Vilar P, Moreno J, Artigas J. Prevalence of coeliac disease in Down’s syndrome. Eur J Gastroenterol Hepatol. 2001;13(3):263–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Anwar AJ, Walker JD, Frier BM. Type 1 diabetes mellitus and Down’s syndrome: prevalence, management and diabetic complications. Diabet Med J Br Diabet Assoc. 1998;15(2):160–3.CrossRefGoogle Scholar
  4. 4.
    Bull MJ. Health Supervision for Children with Down Syndrome. Pediatrics. 2011;128(2):393–406.CrossRefPubMedGoogle Scholar
  5. 5.
    Giménez-Barcons M, Casteràs A, del Armengol ,MP, Porta E, Correa PA, Marín A, et al. Autoimmune predisposition in Down syndrome may result from a partial central tolerance failure due to insufficient intrathymic expression of AIRE and peripheral antigens. J Immunol Baltim Md. 2014;193(8):3872–9.Google Scholar
  6. 6.
    Annah. Thèse sur la trisomie 21 par le Docteur Alamercy [Internet]. Trisomie, vieillissement, accompagnement. [cité 23 mars 2015]. Disponible sur:
  7. 7.
    Ruch W, Schürmann K, Gordon P, Bürgin-Wolff A, Girard J. Coexistent coeliac disease, Graves’ disease and diabetes mellitus type 1 in a patient with down syndrome. Eur J Pediatr. 1985;144(1):89–90.CrossRefPubMedGoogle Scholar
  8. 8.
    Bentley D. A case of Down’s syndrome complicated by retinoblastoma and celiac disease. Pediatrics. 1975;56(1):131–3.PubMedGoogle Scholar
  9. 9.
    Rubio-Tapia A, Hill ID, Kelly CP, Calderwood AH, Murray ,JA. American college of gastroenterology clinical guideline: Diagnosis and management of celiac disease. Am J Gastroenterol. 2013;108(5):656–77.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Persic M, Dessardo S, Subat-Dezulović M, Ahel V. Roz˘manić V. down syndrome and Crohn’s disease: an extremely rare association. Pediatr Int. 2001;43(5):519–21.CrossRefPubMedGoogle Scholar
  11. 11.
    Burgess JN, Kelly KA. Regional enteritis and Down’s syndrome. Minn Med. 1971;54(10):793–4.PubMedGoogle Scholar
  12. 12.
    Muniraj T, Aslanian HR, Farrell J, Jamidar PA. Chronic pancreatitis, a comprehensive review and update. Part II: diagnosis, complications, and management. Dis Mon. 2015;61(1):5–37.CrossRefPubMedGoogle Scholar
  13. 13.
    Freeman HJ. Pancreatic endocrine and exocrine changes in celiac disease. World J Gastroenterol WJG. 2007;13(47):6344–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Carroccio A, Iacono G, Montalto G, Cavataio F, Di Marco C, Balsamo V, et al. Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet. Gut. 1991;32(7):796–9.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Ugazio AG, Maccario R, Notarangelo LD, Burgio GR. Immunology of down syndrome: a review. Am J Med Genet Suppl. 1990;7:204–12.PubMedGoogle Scholar
  16. 16.
    Kusters MAA, Verstegen RHJ, Gemen EFA, de Vries E. Intrinsic defect of the immune system in children with down syndrome: a review. Clin Exp Immunol. 2009;156(2):189–93.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Mårild K, Stephansson O, Grahnquist L, Cnattingius S, Söderman G, Ludvigsson JF. Down syndrome is associated with elevated risk of celiac disease: a nationwide case-control study. J Pediatr. 2013;163(1):237–42.CrossRefPubMedGoogle Scholar
  18. 18.
    Kaukinen K, Partanen J, Mäki M, Collin P. HLA-DQ typing in the diagnosis of celiac disease. Am J Gastroenterol. 2002;97(3):695–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Husby S, Koletzko S, Korponay-Szabó IR, Mearin ML, Phillips A, Shamir R, et al. European Society for Pediatric Gastroenterology, Hepatology, and nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54(1):136–60.CrossRefPubMedGoogle Scholar
  20. 20.
    Corazza GR, Villanacci V. Coeliac disease. J Clin Pathol. 2005;58(6):573–4.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Jevon GP, Madhur R. Endoscopic and histologic findings in pediatric inflammatory bowel disease. Gastroenterol Hepatol. 2010;6(3):174–80.Google Scholar
  22. 22.
    McCarthy DM, Katz SI, Gazze L, Waldmann TA, Nelson DL, Strober W. Selective IgA Deficiency Associated with Total Villous Atrophy of the Small Intestine and an Organ-Specific Anti-Epithelial Cell Antibody. J Immunol. 1978;120(3):932–8.PubMedGoogle Scholar
  23. 23.
    Unsworth DJ, Walker-Smith JA. Autoimmunity in diarrhoeal disease. J Pediatr Gastroenterol Nutr. 1985;4(3):375–80.CrossRefPubMedGoogle Scholar
  24. 24.
    Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol Orlando Fla. 1999;92(1):34–48.CrossRefGoogle Scholar
  25. 25.
    Malamut G, Verkarre V, Suarez F, Viallard J-F, Lascaux A-S, Cosnes J, et al. The enteropathy associated with common variable immunodeficiency: the delineated frontiers with celiac disease. Am J Gastroenterol. 2010;105(10):2262–75.CrossRefPubMedGoogle Scholar
  26. 26.
    Murray JA, Rubio-Tapia A. Diarrhoea due to small bowel diseases. Best Pract Res Clin Gastroenterol. 2012;26(5):581–600.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Greenson JK. The biopsy pathology of non-coeliac enteropathy. Histopathology. 2015;66(1):29–36.CrossRefPubMedGoogle Scholar
  28. 28.
    Gentile NM, Murray JA, Pardi DS. Autoimmune enteropathy: a review and update of clinical management. Curr Gastroenterol Rep. 2012;14(5):380–5.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Kobayashi I, Imamura K, Yamada M, Okano M, Yara A, Ikema S, et al. A 75-kD autoantigen recognized by sera from patients with X-linked autoimmune enteropathy associated with nephropathy. Clin Exp Immunol. 1998;111(3):527–31.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Caviglia GP, Pantaleoni S, Touscoz GA, Adriani A, Rosso C, Smedile A, et al. Fecal calprotectin is an effective diagnostic tool that differentiates inflammatory from functional intestinal disorders. Scand J Gastroenterol. 2014;49(12):1419–24.CrossRefPubMedGoogle Scholar
  31. 31.
    Bouhnik Y. Ac anti-Saccharomyces cerevisiae. Revue Praticien; 2005.Google Scholar
  32. 32.
    Akram S, Murray JA, Pardi DS, Alexander GL, Schaffner JA, Russo PA, et al. Adult autoimmune enteropathy: Mayo Clinic Rochester experience. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2007;5(11):1282–90 .quiz 1245Google Scholar
  33. 33.
    Ram G, Chinen J. Infections and immunodeficiency in down syndrome. Clin Exp Immunol. 2011;164(1):9–16.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Pellegrini FP, Marinoni M, Frangione V, Tedeschi A, Gandini V, Ciglia F, et al. Down syndrome, autoimmunity and T regulatory cells. Clin Exp Immunol. 2012;169(3):238–43.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Skogberg G, Lundberg V, Lindgren S, Gudmundsdottir J, Sandström K, Kämpe O, et al. Altered Expression of Autoimmune Regulator in Infant Down Syndrome Thymus, a Possible Contributor to an Autoimmune Phenotype. J Immunol Author Choice. 2014;193(5):2187–95.CrossRefGoogle Scholar
  36. 36.
    Cuadrado E, Barrena MJ. Immune dysfunction in Down’s syndrome: primary immune deficiency or early senescence of the immune system? Clin Immunol Immunopathol. 1996;78(3):209–14.CrossRefPubMedGoogle Scholar
  37. 37.
    Kusters MA, Verstegen RH, de Vries E. Down Syndrome: Is It Really Characterized by Precocious Immunosenescence? Aging Dis. 2 déc 2011; 2(6):538–45.Google Scholar
  38. 38.
    Sohachi Nanjo JN. Immune-mediated protein-losing enteropathy with down syndrome. Intern Med Tokyo Jpn. 2014;53(20):2301–5.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Anne Depince-Berger
    • 1
  • Clara Cremilieux
    • 2
  • Melanie Rinaudo-Gaujous
    • 1
  • Christian Genin
    • 1
  • Benedicte de Freminville
    • 3
  • Claude Lambert
    • 1
  • J. Bruneau
    • 4
  • Stephane Paul
    • 1
  1. 1.GIMAP EA3064, Laboratory of Immunology and immunomonitoring, CIC CIE3 InsermVaccinologyHopital NordCHU Saint-EtienneFrance
  2. 2.Gastroenterology and Pediatric DepartmentHopital NordCHU Saint-EtienneFrance
  3. 3.Laboratory of GeneticsHopital NordCHU Saint-EtienneFrance
  4. 4.Pathology Department, Hôpital Necker - Enfants Malades, Assistance Publique - Hôpitaux de Paris (APHP), Faculté de Médecine Paris DescartesUniversité Sorbonne Paris CitéParisFrance

Personalised recommendations